AllergiesDE3NCT02017431
Air Pollution and Allergens - Attenuation of Health Effects Particle Reduction
A study testing Allergen, Saline and Particle depleted diesel exhaust in people with Allergies, run by University of British Columbia at 1 site in Canada.
Trial summary
The study probes the effects of combined exposures to diesel exhaust and allergens on lung function and on the immune system, specifically focusing on the ability of a particle depletion technique to attenuate effects we and others have seen previously. Read more about this study
- Who is it for?
- Ages 19 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Allergies
- What is being tested?
- Allergen, Saline and Particle depleted diesel exhaust
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2014to Apr 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 19 and 49 years
- Non-smoking
- Positive skin prick test for at least one of: birch, grass, or dust
Who cannot join
- Using inhaled corticosteroids
- Pregnant or planning to be pregnant in the next 12 months / Breastfeeding
- Usage of bronchodilators more than three times per week.
- Co-morbidities (as assessed by the primary investigator)
- Taking part in other studies
- Unwilling to withhold bronchodilator, aspirin, anti-coagulant, antihistamine or decongestant medications or caffeine prior to testing procedures.
Show all 9Show fewer
- FEV1(Forced expiratory volume in one second) < 70% predicted.
- Allergy to lidocaine, fentanyl, midazolam or salbutamol.
- Unstable asthma (i.e exacerbation in 2 weeks preceding testing)
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: Strengthening the Case for Ongoing Reduction of Exposure to Traffic-Related Air Pollution
The study probes the effects of combined exposures to diesel exhaust and allergens on lung function and on the immune system, specifically focusing on the ability of a particle depletion technique to attenuate effects we and others have seen previously. Individuals are exposed to either filtered air (FA), carefully controlled levels of diesel exhaust (DE) or particle-depleted diesel exhaust (PDDE) in our exposure chamber, after which the investigators will administer an inhaled allergen challenge. 48h later, a procedure called bronchoscopy is used to collect samples from the lungs. After 1 month, the entire procedure is to be repeated with one of the alternate exposures. This will be repeated 4 times (4 exposures; 2 filtered air, 1 diesel exhaust, 1 particle-depleted diesel exhaust)
Read the detailed description
- Purpose/Objective: The aim of this study is to investigate the ability of depletion of diesel exhaust particles to attenuate adverse effects of diesel exhaust on lung function and on allergic responses.
- Hypotheses: Hypothesis 1: Allergen-specific immune response (specific IgG4, etc; relevant responses in DNA methylation and proteomics) in allergen-challenged airways in sensitized individuals is increased by diesel exhaust "synergy". Hypothesis 2: Synergistic responses will be greater in asthmatics than in non-asthmatics. Hypotheses 3: Synergy is attributable to the particulate fraction of DE (i.e. is normalized by particle depletion).
- Justification: Diesel exhaust consists of both gaseous and particulate air pollutants. In recent studies, cardiovascular effects seem attenuated when the particulate portion is removed. We would like to know if that is true for respiratory and immunological endpoints. Understanding these changes may help us prevent health problems associated with air pollution in the future.
- Research Method:
Blinded crossover experiment between four conditions (DE and allergen, PDDE and allergen, FA and allergen, FA and saline), randomized and counter-balanced to order. Each condition will be separated by a 4-week washout period.
An inhaled allergen or saline challenge is delivered after each exposure (DE, PDDE, or FA). 24 h post challenge, airway reactivity will be assessed with a methacholine challenge. 48 h post challenge, bronchoalveolar lavage (BAL), airway brushes and tissue biopsies will be obtained for analysis of immune activation. Nasal lavage samples will also be collected to examine responses in the upper airways and blood and urine will be studied to examine systemic responses. Spirometry and methacholine challenge will be used to assess effects on airway function.
- Conditions
- Allergies
- Being tested
- Allergen, Saline, Particle depleted diesel exhaust
- Keywords
- Diesel exhaust, Particle depleted diesel exhaust, Air pollution, Airway responsiveness, Allergies
- Medical subject headings
- Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllergenOther
Subject specific allergen is inhaled on day 1 of the triad
SalineOther
Saline is inhaled on day 1 of the triad
Particle depleted diesel exhaustOther
High-efficiency particulate filtration of diesel exhaust
| Study group | Role | What they receive |
|---|---|---|
| Filtered air | Active comparator | Exposure for 2 hours to filtered air followed by subject specific inhaled allergen challenge Receives: Other: Allergen |
| Diesel exhaust | Experimental | Exposure for 2 hours to diesel exhaust followed by subject specific inhaled allergen challenge Receives: Other: Allergen |
| Filtered air control | Active comparator | Exposure for 2 hours to filtered air followed by inhaled saline challenge Receives: Other: Saline |
| Particle depleted diesel exhaust | Experimental | Exposure for 2 hours to particle depletion diesel exhaust followed by inhaled allergen challenge Receives: Other: Allergen; Other: Particle depleted diesel exhaust |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune response to allergen +/- DE (BAL)
BAL cellular differential and activation,
Measured: 48 hours
Immune response to allergen +/- DE (Th1/Th2/IgE/IgG4)
Th1/Th2 profile and IgE and IgG4 specific to the allergen used for allergen challenge will be assessed.
Measured: 48 hours
Secondary outcomes (2)
Epithelial cell DNA methylation
Determine if allergen-induced changes in DNA methylation within epithelial cells is augmented by DE (300 µg/m3 inhaled for two hours) and attenuated by PDDE.
Measured: 48 hours
Proteomic signature
Determine if allergen-induced changes in proteomic profile within epithelial cells is augmented by DE (300 µg/m3 inhaled for two hours) and attenuated by PDDE.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2013 (estimated)
- Study startJan 2014
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for AllergiesStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Carlsten, University of British Columbia
- Investigators
- Christopher Carlsten, MD, MPH, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02017431
- Sponsor's protocol ID
- H11-01831/2013
- Acronym
- DE3
- Status last verified
- Sep 2017
- First submitted
- 16 Dec 2013
- Last updated
- 29 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Calhoun WJ, Jarjour NN, Gleich GJ, Stevens CA, Busse WW. Increased airway inflammation with segmental versus aerosol antigen challenge. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1465-71. doi: 10.1164/ajrccm/147.6_Pt_1.1465.
PubMed 8389107Diaz-Sanchez D, Dotson AR, Takenaka H, Saxon A. Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms. J Clin Invest. 1994 Oct;94(4):1417-25. doi: 10.1172/JCI117478.
PubMed 7523450Nordenhall C, Pourazar J, Ledin MC, Levin JO, Sandstrom T, Adelroth E. Diesel exhaust enhances airway responsiveness in asthmatic subjects. Eur Respir J. 2001 May;17(5):909-15. doi: 10.1183/09031936.01.17509090.
PubMed 11488325Carlsten C, Melen E. Air pollution, genetics, and allergy: an update. Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):455-60. doi: 10.1097/ACI.0b013e328357cc55.
PubMed 22885891Riedl MA, Diaz-Sanchez D, Linn WS, Gong H Jr, Clark KW, Effros RM, Miller JW, Cocker DR, Berhane KT; HEI Health Review Committee. Allergic inflammation in the human lower respiratory tract affected by exposure to diesel exhaust. Res Rep Health Eff Inst. 2012 Feb;(165):5-43; discussion 45-64.
PubMed 22852485Robinson A, Huff RD, Ryu MH, Carlsten C. Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study. Respir Res. 2023 Sep 7;24(1):218. doi: 10.1186/s12931-023-02518-y.
PubMed 37679687Ryu MH, Lau KS, Wooding DJ, Fan S, Sin DD, Carlsten C. Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs. Thorax. 2020 Aug;75(8):640-647. doi: 10.1136/thoraxjnl-2020-214561. Epub 2020 May 28.
PubMed 32467339Wooding DJ, Ryu MH, Huls A, Lee AD, Lin DTS, Rider CF, Yuen ACY, Carlsten C. Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study. Am J Respir Crit Care Med. 2019 Sep 1;200(5):565-574. doi: 10.1164/rccm.201809-1657OC.
PubMed 30974969
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strengthening the Case for Ongoing Reduction of Exposure to Traffic-Related Air Pollution
- ClinicalTrials.gov ID
- NCT02017431
- Acronym / sponsor ID
- DE3 / H11-01831/2013
- Conditions
- Allergies
- Keywords
- Diesel exhaust, Particle depleted diesel exhaust, Air pollution, Airway responsiveness, Allergies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 20 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study probes the effects of combined exposures to diesel exhaust and allergens on lung function and on the immune system, specifically focusing on the ability of a particle depletion technique to attenuate effects we and others have seen previously. Individuals are exposed to either filtered air (FA), carefully controlled levels of diesel exhaust (DE) or particle-depleted diesel exhaust (PDDE) in our exposure chamber, after which the investigators will administer an inhaled allergen challenge. 48h later, a procedure called bronchoscopy is used to collect samples from the lungs. After 1 month, the entire procedure is to be repeated with one of the alternate exposures. This will be repeated 4 times (4 exposures; 2 filtered air, 1 diesel exhaust, 1 particle-depleted diesel exhaust)
Detailed description
- Purpose/Objective: The aim of this study is to investigate the ability of depletion of diesel exhaust particles to attenuate adverse effects of diesel exhaust on lung function and on allergic responses.
- Hypotheses: Hypothesis 1: Allergen-specific immune response (specific IgG4, etc; relevant responses in DNA methylation and proteomics) in allergen-challenged airways in sensitized individuals is increased by diesel exhaust "synergy". Hypothesis 2: Synergistic responses will be greater in asthmatics than in non-asthmatics. Hypotheses 3: Synergy is attributable to the particulate fraction of DE (i.e. is normalized by particle depletion).
- Justification: Diesel exhaust consists of both gaseous and particulate air pollutants. In recent studies, cardiovascular effects seem attenuated when the particulate portion is removed. We would like to know if that is true for respiratory and immunological endpoints. Understanding these changes may help us prevent health problems associated with air pollution in the future.
- Research Method:
Blinded crossover experiment between four conditions (DE and allergen, PDDE and allergen, FA and allergen, FA and saline), randomized and counter-balanced to order. Each condition will be separated by a 4-week washout period.
An inhaled allergen or saline challenge is delivered after each exposure (DE, PDDE, or FA). 24 h post challenge, airway reactivity will be assessed with a methacholine challenge. 48 h post challenge, bronchoalveolar lavage (BAL), airway brushes and tissue biopsies will be obtained for analysis of immune activation. Nasal lavage samples will also be collected to examine responses in the upper airways and blood and urine will be studied to examine systemic responses. Spirometry and methacholine challenge will be used to assess effects on airway function.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Filtered air | Active comparator | Other: AllergenExposure for 2 hours to filtered air followed by subject specific inhaled allergen challenge |
| Diesel exhaust | Experimental | Other: AllergenExposure for 2 hours to diesel exhaust followed by subject specific inhaled allergen challenge |
| Filtered air control | Active comparator | Other: SalineExposure for 2 hours to filtered air followed by inhaled saline challenge |
| Particle depleted diesel exhaust | Experimental | Other: Allergen, Other: Particle depleted diesel exhaustExposure for 2 hours to particle depletion diesel exhaust followed by inhaled allergen challenge |
Who may qualify
- Ages
- 19 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age between 19 and 49 years
- Non-smoking
- Positive skin prick test for at least one of: birch, grass, or dust
Key exclusion criteria (9 listed)
- Using inhaled corticosteroids
- Pregnant or planning to be pregnant in the next 12 months / Breastfeeding
- Usage of bronchodilators more than three times per week.
- Co-morbidities (as assessed by the primary investigator)
- Taking part in other studies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllergenSubject specific allergen is inhaled on day 1 of the triad | Other | Diesel exhaust, Filtered air, Particle depleted diesel exhaust |
| SalineSaline is inhaled on day 1 of the triad | Other | Filtered air control |
| Particle depleted diesel exhaustHigh-efficiency particulate filtration of diesel exhaust | Other | Particle depleted diesel exhaust |
Primary outcome
Immune response to allergen +/- DE (BAL)
Time frame: 48 hours
BAL cellular differential and activation,
Immune response to allergen +/- DE (Th1/Th2/IgE/IgG4)
Time frame: 48 hours
Th1/Th2 profile and IgE and IgG4 specific to the allergen used for allergen challenge will be assessed.
2 secondary outcomes
Epithelial cell DNA methylation
Time frame: 48 hours
Proteomic signature
Time frame: 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Background: PubMed 8389107Calhoun WJ, Jarjour NN, Gleich GJ, Stevens CA, Busse WW. Increased airway inflammation with segmental versus aerosol antigen challenge. Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1465-71. doi: 10.1164/ajrccm/147.6_Pt_1.1465.
- Background: PubMed 7523450Diaz-Sanchez D, Dotson AR, Takenaka H, Saxon A. Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms. J Clin Invest. 1994 Oct;94(4):1417-25. doi: 10.1172/JCI117478.
- Background: PubMed 11488325Nordenhall C, Pourazar J, Ledin MC, Levin JO, Sandstrom T, Adelroth E. Diesel exhaust enhances airway responsiveness in asthmatic subjects. Eur Respir J. 2001 May;17(5):909-15. doi: 10.1183/09031936.01.17509090.
- Results publication: PubMed 22885891Carlsten C, Melen E. Air pollution, genetics, and allergy: an update. Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):455-60. doi: 10.1097/ACI.0b013e328357cc55.
- Results publication: PubMed 22852485Riedl MA, Diaz-Sanchez D, Linn WS, Gong H Jr, Clark KW, Effros RM, Miller JW, Cocker DR, Berhane KT; HEI Health Review Committee. Allergic inflammation in the human lower respiratory tract affected by exposure to diesel exhaust. Res Rep Health Eff Inst. 2012 Feb;(165):5-43; discussion 45-64.
- Derived from this study: PubMed 37679687Robinson A, Huff RD, Ryu MH, Carlsten C. Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study. Respir Res. 2023 Sep 7;24(1):218. doi: 10.1186/s12931-023-02518-y.
- Derived from this study: PubMed 32467339Ryu MH, Lau KS, Wooding DJ, Fan S, Sin DD, Carlsten C. Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs. Thorax. 2020 Aug;75(8):640-647. doi: 10.1136/thoraxjnl-2020-214561. Epub 2020 May 28.
- Derived from this study: PubMed 30974969Wooding DJ, Ryu MH, Huls A, Lee AD, Lin DTS, Rider CF, Yuen ACY, Carlsten C. Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study. Am J Respir Crit Care Med. 2019 Sep 1;200(5):565-574. doi: 10.1164/rccm.201809-1657OC.
Related trials for Allergies
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Carlsten, MD, MPH principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Allergen, Saline and Particle depleted diesel exhaust in people with Allergies, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune response to allergen +/- DE (BAL) (time frame: 48 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02017431, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017.